Fast-Dissolving Sodium Alginate-Based Microneedle Patch Integrating Tranilast and Glabridin-Loaded Nanoparticles for Dual-Action Hypertrophic Scar Therapy

Hypertrophic scars (HSs) are a prevalent skin condition that imposes substantial functional, financial, and aesthetic burdens, with existing treatments often leading to recurrence, pain, and adverse effects. To address these issues, we propose a first-in-class fast-dissolving sodium alginate-based microneedle patch (sMN) that achieves sequential, dual-release kinetics by integrating tranilast (TS) and glabridin (GL)-loaded nanoparticles (GLNPs), termed TS+GLNPs@sMN. Our system uniquely integrates rapid TS release for immediate “OFF” switching, suppression of fibroblast activation, stabilization of mast cells, and relief of pruritus, with sustained GL release from GLNPs for prolonged “ON” switching, which promotes fibroblast apoptosis and modulates scar matrix deposition. This sequential “OFF-to-ON” paradigm mirrors the temporal progression of HS pathophysiology, with early inflammatory events preceding fibrotic remodeling. The cone-shaped microneedle patch (~565 μm) demonstrated efficient skin penetration/recovery, even drug distribution, fast dissolution (180 ± 20 s), high loading capacity, and desirable release kinetics. In vitro evaluations confirmed promising anti-proliferative, anti-migratory, and anti-angiogenic effects. Preliminary in vivo biocompatibility in mice was satisfactory, with no skin irritation and normal complete blood count, renal, and hepatic function. In vivo studies in a rabbit ear HS model demonstrate accelerated HS healing, reduced HS thickness, epidermal thickness index (ETI), scar elevation index (SEI), and collagen deposition, along with decreased profibrotic markers, inflammatory cytokines, and angiogenic factors. Overall, the TS+GLNPs@sMN patch offers a minimally invasive, self-administrable, dual-action therapeutic strategy for enhanced HS management, with safety and efficacy in preclinical models.